Uridine Triacetate as Antidote for Patients at Excess Risk of 5-FU Toxicity Due to Overdosage or Impaired Elimination

Expanded access is currently available for this treatment.
Verified March 2014 by Wellstat Therapeutics
Sponsor:
Information provided by (Responsible Party):
Wellstat Therapeutics
ClinicalTrials.gov Identifier:
NCT01432301
First received: September 8, 2011
Last updated: March 10, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to provide uridine triacetate as an antidote to treat patients at excess risk of 5-fluorouracil (5-FU) toxicity due to overdosage (defined as administration of 5-FU at a dose, or infusion rate, greater than the MTD for the patient's intended regimen) or impaired elimination. This study will evaluate survival for 30 days in patients treated with uridine triacetate, initiated between 3 and 96 hours after completion of 5-FU dosing, who are at excess risk of toxicity due to overdosage or impaired elimination. The study will also assess the occurrence, severity, and duration of toxicities known to be associated with 5-FU overdosage or impaired elimination.


Condition Intervention
Toxicity Due to Chemotherapy
Impaired 5FU Elimination
Drug: uridine triacetate

Study Type: Expanded Access     What is Expanded Access?
Official Title: An Open-Label Protocol for the Use of Uridine Triacetate as an Antidote to Treat Patients at Excess Risk of 5-Fluorouracil Toxicity Due to Overdosage or Impaired Elimination

Resource links provided by NLM:


Further study details as provided by Wellstat Therapeutics:

Intervention Details:
    Drug: uridine triacetate
    uridine triacetate granules, 10gms, q6H x 20 doses
    Other Name: PN401
Detailed Description:

Demographics, baseline disease information, prior disease-directed therapy including 5-FU, and details of the 5-FU overexposure (dose, cause, and timing) will be collected. In addition, the occurrence, severity, and duration of neutropenia, thrombocytopenia, leukopenia, mucositis, diarrhea, and skin and neurological toxicities, commonly associated with 5-FU dosing, will be assessed. Vital signs, laboratory values, and adverse events information will be collected and recorded. Systemic levels of uridine and uracil will be evaluated from the available plasma samples of treated patients. Patients will be followed for 30 days unless the patient expires or resumes chemotherapy within the 30 day period.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Criteria

Inclusion Criteria:

  • Excess risk of toxicity due to overdosage (defined as administration of 5-FU at a dose, or infusion rate, greater than the MTD for the patient's intended regimen) of 5-FU, or impaired elimination. Impaired elimination or unusual susceptibility to 5-FU must be documented by one of the following methods:

    • plasma 5-FU levels >10 µM more than 3 hours following cessation of 5-FU dosing
    • previous medical history from earlier 5-FU chemotherapy regimens that indicated unusual susceptibility to 5-FU toxicity, within 7-10 days of receiving 5-FU, such as Grade 3-4 diarrhea, Grade 3-4 mucositis, or Grade 4 neutropenia
    • leukocyte DPD enzyme activity <70% of that observed in the normal population (10 ± 3.4 nmol/hr)
    • presence of deleterious mutations in the DPD gene known to reflect reduced DPD activity and consequent increased risk of 5-FU toxicity
    • plasma uracil/dihydrouracil ratio greater than 2.0
    • early onset or unusual susceptibility (hypersensitivity) to 5-FU toxicity such as Grade 3-4 diarrhea, Grade 3-4 mucositis, Grade 3-4 neutropenia, Grade 3-4 neurological toxicities, or severe, sudden onset cardiotoxicity
  • Judged by the Investigator to have the initiative and means to be compliant with the protocol
  • Able to take oral medications
  • Age ≥ 18 years
  • Able to start treatment with uridine triacetate between 3 and 96 hours after the overdose
  • Provides written informed consent (patient or legally authorized representative)

Exclusion Criteria:

  • Has a known allergy to uridine triacetate or any of its excipients
  • Does not have the initiative and means to be compliant with the protocol
  • Unable to be compliant with taking oral medications
  • More than 96 hours have elapsed since the completion of 5-FU dosing
  • Unable to provide written informed consent (patient or legally authorized representative)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01432301

Contacts
Contact: Robert Tremmel, PharmD 443-831-5626 rtremmel@wellstattherapeutics.com
Contact: William E. Gannon, MD 202-548-4930 WGannon@capcitytek.com

Sponsors and Collaborators
Wellstat Therapeutics
  More Information

No publications provided

Responsible Party: Wellstat Therapeutics
ClinicalTrials.gov Identifier: NCT01432301     History of Changes
Other Study ID Numbers: 401.10.001
Study First Received: September 8, 2011
Last Updated: March 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Wellstat Therapeutics:
5FU overdose
5FU toxicity
Impaired 5FU elimination

Additional relevant MeSH terms:
Antidotes
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 19, 2014